Unexpected roles for radial glial cells during the development of the cerebral cortex

The vast majority of neurons present in the adult brain are produced embryonically during a brief but intense period of neuronal proliferation. Our understanding of this proliferative embryonic period has undergone major revision during recent years. Work from our laboratory and others has shown that a specialized cell type known as the radial glial cell plays an unexpected but fundamental role in neuronal production. Present transiently during development, radial glial cells may be in part responsible for the unique proliferative capacity of the embryonic brain.; During neural development, radial glial cells line the cerebral ventricles, where their classic elongated morphology provides a scaffold for newborn neurons migrating into the cortex. Their role in supporting neuronal migration was traditionally believed to represent the primary function of radial glial cells during development. However, recent work from our laboratory has shown that radial glia can also function as neuronal stem cells, resulting in the production of cortical neurons. In fact, it now appears that most cortical neurons may derive from radial glia. These findings represent a fundamental frame-shift in the field of developmental neurobiology, since neurons and glia are traditionally presumed to arise from separate cell lineages. Importantly, radial glial cells appear to be capable of much more than mere structural support.; That radial glial cells play multiple roles during development raises the possibility that radial glial signaling mechanisms could potentially regulate both neuronal production and neuronal migration. However, very little is known about radial glial signaling. Using calcium imaging methods, we have demonstrated that spontaneous calcium waves propagate through radial glial cells of the proliferative ventricular zone. Disruption of radial glial calcium waves can modulate cell proliferation during the peak of embryonic neurogenesis, suggesting that this novel radial glial signaling mechanism may help to regulate cortical neuronal production.; The function of radial glial cells extends well beyond their traditional role in supporting neuronal migration. We have shown that radial glial cells are key neuronal progenitors, producing clones of neuronal progeny that then migrate along parental radial glial fibers into the cortex. Furthermore, radial glial cells are capable of signaling to each other via robust calcium waves that may regulate levels of neuronal production. This work demonstrates that radial glia are not simply passive cables along which neurons migrate, but are in fact active, dynamic cells that can instruct and coordinate cortical architecture. These surprising findings provide an important new perspective from which to investigate the complex mechanisms underlying neural development.